Effect of interleukin 17 on proteoglycan degradation in murine knee joints
Effect of interleukin 17 on proteoglycan degradation in murine knee joints
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DOI：
10.1136/ard.59.7.529
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发表时间：
2000-07-01
影响因子：
27.4
通讯作者：
So, A
中科院分区：
文献类型：
--
作者：
Dudler, J;Renggli-Zulliger, N;So, A
目的：探讨白细胞介素17 （il - 17）在小鼠膝关节内直接注射对软骨分解代谢和关节炎症的影响。方法：对正常C57 B1小鼠膝关节进行1次或多次注射重组il - 17或il - 1 β。通过高锝-99m （Tc-99）摄取和组织切片的组织学评分来评估炎症。通过红花素O染色切片的组织学评分来评估蛋白多糖的消耗。研究了(SO4)-S-35掺入对蛋白多糖合成的影响。结果：单次关节内注射il - 17 （10 ng/膝盖）产生的效果与il - 1 β （10 ng/膝盖）非常相似。服用Tc-99 6小时或24小时未发现炎症。然而，红花素O染色显示蛋白多糖在48小时耗尽。组织学评分显示，反复注射IL17可引起关节炎症和软骨蛋白聚糖耗竭。与IL1 β不同，IL17诱导的蛋白聚糖耗损似乎只是降解增加的结果，因为没有观察到(SO4)-S-35掺入的抑制。结论：在体内，这些发现证实了il - 17对软骨的分解代谢作用。因此，除了对巨噬细胞和滑膜细胞有刺激作用外，IL17是第一个对软骨有直接分解代谢作用的T细胞细胞因子，使其成为关节炎发病过程中潜在的重要细胞因子。
Objective-To evaluate the effect of murine interleukin 17 (IL17) on cartilage catabolism and joint inflammation by direct intra-articular injection of the cytokine into murine knee joints.Methods-Knees of normal C57 B1 mice were injected once or repeatedly with recombinant IL17 or IL1 beta. Inflammation was estimated by technetium-99m pertechnetate (Tc-99) uptake and histological scoring of tissue sections. Proteoglycan depletion was evaluated by histological scoring of safranin O stained sections. Effects on proteoglycan synthesis were studied by (SO4)-S-35 incorporation.Results-A single intra-articular injection of IL17 (10 ng/knee) produced effects very similar to those of IL1 beta (10 ng/knee). No inflammation was detected at six or 24 hours by Tc-99 uptake. However, safranin O staining showed depletion of proteoglycan at 48 hours. Repeated injections of IL17 induced joint inflammation and cartilage proteoglycan depletion as shown by histological scoring. Unlike IL1 beta, proteoglycan depletion induced by IL17 seemed to be the result of increased degradation only, as no suppression of (SO4)-S-35 incorporation was seen.Conclusion-These findings confirm, in vivo, the catabolic effects of IL17 on cartilage. IL17 is thus the first T cell cytokine showing a direct catabolic effect on cartilage in addition to stimulatory effects on macrophages and synoviocytes, making it a potentially important cytokine in the pathogenesis of arthritis.